Domain-domain motions in proteins from time-modulated pseudocontact shifts.

In recent years paramagnetic NMR derived structural constraints have become increasingly popular for the study of biomolecules. Some of these are based on the distance and angular dependences of pseudo contact shifts (PCSs). When modulated by internal motions PCSs also become sensitive reporters on molecular dynamics. We present here an investigation of the domain-domain motion in a two domain protein (PA0128) through time-modulation of PCSs. PA0128 is a protein of unknown function from Pseudomonas aeruginosa (PA) and contains a Zn(2+) binding site in the N-terminal domain. When substituted with Co(2+) in the binding site, several resonances from the C-terminal domain showed severe line broadening along the (15)N dimension. Relaxation compensated CPMG experiments revealed that the dramatic increase in the (15)N linewidth came from contributions of chemical exchange. Since several sites with perturbed relaxation are localized to a single beta-strand region, and since extracted timescales of motion for the perturbed sites are identical, and since the magnitude of the chemical exchange contributions is consistent with PCSs, the observed rate enhancements are interpreted as the result of concerted domain motion on the timescale of a few milliseconds. Given the predictability of PCS differences and the easy interpretation of the experimental results, we suggest that these effects might be useful in the study of molecular processes occurring on the millisecond to microsecond timescale.

[Molecular dynamics of oligopeptides. 2. Dynamic correlation functions of the conformational modes of the modified dipeptides]. / Molekuliarnaia dinamika oligopeptidov. 2.Korreliatsionnye funktsii vnutrennikh stepenei svobody modifitsirovannykh dipeptidov.

The method of investigation of dynamic correlation functions in molecules with conformational mobility on an example of modified dypeptides by molecular dynamics is proposed. Comparison of results for different types torsion angles and internuclear distances are carried out. Connection between the chemical structure of peptides and the peculiarities of internal dynamic correlations is established. A question about dynamic isomorphism of amino acids is discussed.

[Molecular dynamics of oligopeptides. 1. The use of long trajectory and high temperature data for determination of statistical weight of conformational substates]. / Molekuliarnaia dinamika oligopeptidov. 1. Ispol'zovanie dannykh traektorii i vysokikh temperatur dlia opredeleniia statisticheskogo vesa konformatsionnykh podsostoianii.

The method of molecular dynamics investigations of the particularities of macromolecule physical-chemical properties is discussed. The results, obtained from the calculations of modified dipeptides in different regimes (different temperatures, length of trajectories and ways of thermostat simulation) are compared. The optimal conditions for this peptides calculations are determined: collisional dynamics regime, trajectories not less than 5000 ps, temperature about 1000 K. In this case the figurative point is able to scan the molecule configuration space and the statistically reliable results could be obtained.